Evaluation of effects of chitosan in preventing hemorrhagic cystitis in rats induced by cyclophosphamide

Abstract

100mg/kgのcyclophosphamideを腹腔内投与することにより, 出血性膀胱炎を誘発し, chitosan (0.3ml)を膀胱内注入し, 検討した結果, cyclophosphamide投与1時間後の投与群において死亡率の減少と, 肉眼的膀胱出血, 壊死および炎症の発生率の低下が認められた。膀胱炎発生後のchitosan膀胱内注入は, 特に繰り返し施行した場合, cyclophosphamideによる変化を悪化させる傾向がみられた。cyclophosphamide投与1時間後の投与群では, chitosanは出血性膀胱炎の発生を抑制する可能性が示唆された。さらに, cyclophosphamideによる腎の変化も認められた

Hemorrhagic cystitis is a common problem following cyclophosphamide or radiation therapy. Chitosan has been shown to be an effective hemostatic agent and promoter of wound healing in animal experiments. We evaluated the safety and efficacy of intravesical chitosan in an animal model of cyclophosphamide cystitis. Hemorrhagic cystitis was induced in female F344 rats by intraperitoneal cyclophosphamide, 100 mg/kg. Chitosan solution (0.3 ml) was instilled intravesically on day 1 (Group 1), on days 1, 3, and 5 (Group 2), or 1 hour after the administration of cyclophosphamide (Group 3). The rats in group 4 were treated with chitosan diluent on day 1 after cyclophosphamide, and the rats in group 5 received intravesical chitosan without cyclophosphamide. Sequential examination revealed decreased mortality and lower incidences of severe bladder bleeding, necrosis and inflammation in Group 3. Treatment delayed until after the appearance of the cystitis, especially repeated treatments, appeared to make the cyclophosphamide-induced changes worse. Used within 1 hour of cyclophosphamide administration, before the cystitis develops, chitosan seemed to have the possibility to inhibit the appearance of hemorrhagic cystitis. In addition to the changes in the bladder, severe changes occurred in the kidneys secondary to cyclophosphamide.